Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling

Blood. 2008 Oct 15;112(8):3164-74. doi: 10.1182/blood-2008-03-144956. Epub 2008 Aug 6.


Megakaryocyte (MK) is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, which was a process considered to be an incomplete mitosis aborted in anaphase. Here, we used time-lapse confocal video microscopy to visualize the endomitotic process of primary human megakaryocytes. Our results show that the switch from mitosis to endomitosis corresponds to a late failure of cytokinesis accompanied by a backward movement of the 2 daughter cells. No abnormality was observed in the central spindle of endomitotic MKs. A furrow formation was present, but the contractile ring was abnormal because accumulation of nonmuscle myosin IIA was lacking. In addition, a defect in cell elongation was observed in dipolar endomitotic MKs during telophase. RhoA and F-actin were partially concentrated at the site of furrowing. Inhibition of the Rho/Rock pathway caused the disappearance of F-actin at midzone and increased MK ploidy level. This inhibition was associated with a more pronounced defect in furrow formation as well as in spindle elongation. Our results suggest that the late failure of cytokinesis responsible for the endomitotic process is related to a partial defect in the Rho/Rock pathway activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Antigens, CD34 / biosynthesis
  • Cell Separation
  • Cytokinesis
  • Humans
  • Lentivirus / metabolism
  • Megakaryocytes / cytology*
  • Microscopy, Confocal
  • Microscopy, Video
  • Mitosis*
  • Ploidies
  • Signal Transduction
  • Telophase
  • rho-Associated Kinases / metabolism*


  • Actins
  • Antigens, CD34
  • rho-Associated Kinases